The Number of Metastatic Lymph Nodes and the Ratio Between Metastatic and Examined Lymph Nodes Are Independent Prognostic Factors in Esophageal Cancer Regardless of Neoadjuvant Chemoradiation or Lymphadenectomy Extent

Department of Digestive and Oncological Surgery, University Hospital C Huriez, Centre Hospitalier Régional Universitaire, Lille, France.
Annals of Surgery (Impact Factor: 8.33). 03/2008; 247(2):365-71. DOI: 10.1097/SLA.0b013e31815aaadf
Source: PubMed


To investigate whether the number of lymph nodes metastasis (LNMs) and the ratio between metastatic and examined lymph nodes (LNs) are better prognostic factors when compared with traditional staging systems in patients with esophageal carcinoma.
The accuracy of the 6th UICC/TNM classification is suboptimal, especially when not taking into account neoadjuvant therapy and lymphadenectomy extent.
For 536 patients who underwent curative en bloc esophagectomy, in whom 51.5% (n = 276) received neoadjuvant chemoradiation, LNMs were classified according to the 6th UICC/TNM classification and systems based on the number (< or =4 and >4) or the ratio (< or =0.2 and >0.2) of LNMs. Survival of the respective stages, predictors of survival, and influence of both chemoradiation and number of examined LNs were studied.
After a median follow-up of 50 months, the 5-year survival rates were 47% for the entire population, significantly poorer for patients with >4 LNMs (8% vs. 53%, P < 0.001) or a ratio of LNMs >0.2 (22% vs. 54%, P < 0.001). After adjustment for confounding variables, a number of LNMs >4 and a ratio of LNMs >0.2 were the only predictors of poor prognosis. The prognostic role of both the number and the ratio of LNMs was maintained whether patients received neoadjuvant chemoradiation or not. Moreover, LN ratio is shown to be more accurate for inadequately staged patients (<15 examined LNs), whereas the number of LNMs is pertinent for adequately staged patients (> or =15 examined LNs).
Staging systems for esophageal cancer that use the number (< or =4 or >4) and the ratio (< or =0.2 or >0.2) of LNMs have greater prognostic importance than the current staging systems because of the good stratification of the groups and their clinical utility, taking into account neoadjuvant therapy and lymphadenectomy extent.

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    • "Several studies have identified different risk factors of tumor recurrence after surgery of oesophageal cancer. Positive lymph node status is the most frequent factor identified [7-9]. It is also highlighted as an independent risk factor in our study. "
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    ABSTRACT: The aim of this study was to analyze the profile of tumor recurrence for patients operated on for cancer of oesophagogastric junction or oesophagus by Ivor-Lewis oesophagectomy. Patients undergoing potentially curative Ivor-Lewis oesophageal resection between January 1999 to December 2008 at a single center institution were retrospectively analyzed. Their clinical records, details of surgical procedure, postoperative course, pathological findings, recurrence and long term survival were reviewed retrospectively. Univariate and multivariate survival analyses were performed. One hundred and twenty patients were analyzed. Fifty three patients (44%) presented recurrence during median follow-up of 58 months. Five-year relapse free survival (RFS) rate was 51% (95%CI = [46; 65%]). On multivariate analysis, pT stage > 2 (HR = 2.42, 95%CI = [1.22; 4.79] p = 0.011), positive lymph node status (HR = 3.69; 95% CI = [1.53; 8.96] p = 0.004) and lymph node ratio > 0.2 (HR = 2.57; 95%CI = [1.38; 4.76] p = 0.003) were associated with a poorer RFS and their combination was correlated to relapse risk. Moreover, preoperative tumor stenosis was associated with an increased risk of local recurrence (HR = 3.46; 95% CI = [1.38; 8.70] p = 0.008) whereas poor or undifferentiated tumor was associated with an increased risk of distant recurrence (HR = 3.32; 95% CI = [1.03; 10.04] p = 0.044). pT stage > 2, positive lymph node status and lymph node ratio > 0.2 are independent prognostic factors of recurrence after Ivor-Lewis surgery for cancer. Their combination is correlated with an increasing risk of recurrence that may argue favorably, in addition with preoperative tumor stenosis assessment, for adjuvant treatment or reinforced follow-up.
    Full-text · Article · Nov 2013 · Journal of Cardiothoracic Surgery
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    • "This suggests that the new staging system may be not applicable to Asian patients with esophageal squamous cell carcinoma (ESCC) because it does not accurately predict their prognosis and therefore may not provide reliable selection of the most appropriate adjuvant therapy. Several studies in Asia have demonstrated that dissection of a large number of lymph nodes is helpful for accurate staging [9–11]. Current recommendations suggest that at least 18 lymph nodes be dissected [12]. "
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    ABSTRACT: The objective of this study was to investigate the number of metastatic lymph nodes (pN) and the metastatic lymph node ratio (MLR) on the post-surgical prognosis of Chinese patients with esophageal cancer (EC) and lymph node metastasis. We enrolled 353 patients who received primary curative resection for EC from 1990 to 2003. The association of pN and MLR with 5-year overall survival (OS) was examined by receiver operating characteristic (ROC) and area under the curve (AUC) analysis. The Kaplan-Meier method was used to calculate survival rates, and survival curves were compared with the log-rank test. The Cox model was employed for univariate and multivariate analyses of factors associated with 5-year OS. The median follow-up time was 41 months, and the 1-, 3- and 5-year OS rates were 71.2%, 30.4%, and 19.5%, respectively. Univariate analysis showed that age, pN stage, and the MLR were prognostic factors for OS. Patients with MLRs less than 0.15, MLRs of 0.15-0.30, and MLRs greater than 0.30 had 5-year OS rates of 30.1%, 17.8%, and 9.5%, respectively (p < 0.001). Patients classified as pN1, pN2, and pN3 had 5-year OS rates of 23.7%, 11.4%, and 9.9%, respectively (p < 0.001). Multivariate analysis indicated that a high MLR and advanced age were significant and independent risk factors for poor OS. Patients classified as pN2 had significantly worse OS than those classified as pN1 (p = 0.022), but those classified as pN3 had similar OS as those classified as pN1 (p = 0.166). ROC analysis indicated that MLR (AUC = 0.585, p = 0.016) had better predictive value than pN (AUC = 0.565, p = 0.068). The integrated use of MLR and pN may be suitable for evaluation of OS in Chinese patients with EC and positive nodal metastasis after curative resection.
    Full-text · Article · Sep 2013 · PLoS ONE
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    • "In surgical series, the rate of ypT0N0M0 (i.e. pathologic CR) after preoperative CRT is about 20–30%% [4,18,19], and this group of patients may achieve an excellent 5-year survival as high as 55%, with the best outcome for younger patients [19]. Using clinical tools–with their poor sensitivity–for clinical restaging, results from some studies showed that clinical CR (cCR) rates varied from 30% to 62% [10,11,20-22], depending on the time period of treatment, imaging modalities (with or without post treatment biopsies), and, obviously, on treatments. "
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    ABSTRACT: To identify predictors of long-term outcome for patients with clinical complete response (cCR) after definite chemoradiotherapy (CRT) or radiation therapy (RT) for oesophageal cancer (EC). In this retrospective study, we reviewed the files of all patients from our institution that underwent definitive RCT or RT for EC, from January 1998 to December 2003. Among 402 consecutive patients with EC, 110 cCR responses were observed, i.e. without evidence of tumour on morphological examination of the biopsy specimens, 8 to 10 weeks after radiation. Baseline patient and tumour characteristics were as follows: male = 98/110, median age = 60, squamous histology = 103/110, tumour site (upper/middle/lower third) = 41/50/19, weight loss none/<10%/>=10% = 36/45/29, dysphagia grade 1/2/>=3 = 30/14/66. Patients were staged according to endosonography and/or computed tomography. There were 9 stage I, 31 stage IIA, 15 stage IIB, 41 stage III, 6 stage IV. Post treatment nutritional characteristics were as follows: weight loss during treatment none/<10% >= 10% = 35/38/37, remaining dysphagia grade 1/2/>=3 = 54/24/32. Univariate and multivariate analyses were performed using log-rank and Cox proportional hazards models, and survival curves were estimated using the Kaplan-Meier method. During follow up (median: 6 [0.4--9.8] years), 16 patients had salvage surgery. Median OS was 2.5 years, and 5-year OS was 33.5%. Histological type, stage, age, gender, and treatment characteristics had no significant impact on outcome. The risk of death was increased two-fold for patients with grade >= 3 dysphagia after treament (HR = 1.9 [1.2--3.1], p = 0.007). Weight loss >=10% during treatment also negatively affected outcome (HR = 1.8 [1.0--3.2], p = 0.040). One EC patient among 3 with cCR after definite CRT/RT is still alive at 5 years. Variables related to reduced OS were: remaining significant dysphagia after treatment and weight loss >=10% during treatment.
    Full-text · Article · Sep 2013 · BMC Cancer
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